The primary objective of this project is to determine whether the cotton rat, which has proved highly susceptible to a number of viruses that infect humans, can be infected with HIV-1 and thus be a small animal model to investigate aspects of infection that are difficult and expensive to study in humans or an animal model such as the chimpanzee. The initial experiments, using LAI, a laboratory-adapted strain of HIV-1, were done in the two inbred species of cotton rats, Sigmodon fulviventor and S. hispidus . This study demonstrated that S. fulviventor is the more susceptible, and that all the animals of this species tested in the initial studies were infected as determined by PCR and antibody assays. Although infectious virus could not be isolated directly from the blood of these infected animals, PCR clearly detected the virus in the cultured cells. Moreover, the virus was passaged four times serially in cotton rats starting with blood from one PCR-positive animal. A second experiment was initiated using a fresh human isolate of HIV-1, strain #101, inoculated into the retro-orbital sinus of 19 S. fulviventors. All of the animals were shown to become PCR-positive using peripheral blood mononuclear cells by 28 weeks after viral inoculation. Although all animals became infected, in two cotton rats that were sacrificed 24 weeks after infection only minor pathological spleenic changes were observed despite finding that all organs tested were PCR positive. In an effort to obtain a small animal model in which HIV-1 is pathogenic an experiment has been initiated to infect new-born S. fulviventor cotton rats.